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Biomedical subjects

A Imai

Publications and source records attributed to A Imai.

At least 109 records · Page 6Linked to original sources

Evidence for tight coupling of gonadotropin-releasing hormone receptors to phosphatidylinositol kinase in plasma membrane from ovarian carcinomas.

Gonadotropin-releasing hormone (Gn-RH) analogs inhibit ovarian cancer cell proliferation in vivo and in vitro. To examine whether Gn-RH receptor (Gn-RHR) mediates direct antiproliferative effects, we attempted to determine inhibitory regulation by Gn-RH of phosphatidylinositol (PtdIns) kinase activity, known to stimulate mitogenic response, in plasma membranes isolated from ovarian carcinoma samples. Ovarian carcinomas surgically removed and cloned cell line SK-OV3 had been screened for Gn-RHR expression prior to plasma membrane isolation. PtdIns kinase activity was measured as phosphorylation of exogenous substrate PtdIns by the purified plasma membranes. Incubation of the plasma membranes isolated from Gn-RHR-positive specimens with [gamma-32P]ATP and PtdIns caused [32P]phosphate incorporation into PtdIns phosphate (PtdInsP) in a time-dependent manner. Concomitant exposure of the membrane preparations to Gn-RH analog buserelin (1 microM) led to a 70% inhibition of the PtdInsP production, when compared to control. After 10 or 15 min of an initial incubation, the addition of analog resulted in similar suppression of PtdIns phosphorylation. This inhibition was dependent on the buserelin dose, and a half-maximal effect occurred at a concentration 0.1 to 1 nM of buserelin. Degradation of the produced PtdInsP in the plasma membranes was not affected by the Gn-RH analog. Similar inhibition of PtdIns kinase activities was observed in membranes prepared from cells that had been pretreated with buserelin (1 microM) for 48 hr prior to assay. These findings demonstrate that PtdIns kinase activity is suppressed by Gn-RH analog in plasma membrane isolated from GnRHR-expressing ovarian carcinomas, suggesting a tight coupling of Gn-RHR to PtdIns. The inhibition of membrane-associated PtdIns kinase by Gn-RHR occupancy may mediate the antimitogenic action of the hormone on human ovarian carcinomas.

1-Phosphatidylinositol 4-Kinase↗

Successful pregnancy in a patient with pseudomyxoma peritonei arising from ovarian mucinous cystadenocarcinoma treated with cisplatin.

A 24-year-old Japanese woman clinically showing pseudomyxoma peritonei arising from ovarian mucinous cystadenocarcinoma FIGO stage Ic is reported. She received intra-abdominal administrations of cisplatin five times following left oophorectomy. After being free of disease for 6 months, she conceived and carried two pregnancies to successful deliveries at 34 and 37 weeks, respectively. At the Cesarean sections, there were no abnormal findings except for right ovarian mucinous cystadenoma. She has had no evidence of recurrence by the time of the 60-month postoperative examination.

Abdomen↗

Immunoglobulin free light chain assay using latex agglutination.

Under normal biological conditions, immunoglobulin light chains are generally formed in conjunction with heavy chains; however, small quantities of free light chains are also produced. Thus, two types of immunoglobulin light chains may be identified; immunoglobulin-bound light chains and free light chains. In mature neoplastic B cells, immunoglobulin synthesis, including that of the free light chain, is generally increased. Furthermore, elevated free light chain levels also occur in the presence of renal glomerular and tubular impairment. Thus, the quantitative and qualitative measurement of free light chains is of considerable clinical benefit. Although methods for measurement of free light chains do exist they are technically complicated and time consuming. Previously, we have reported a quantitative nephelometric immunoassay for measuring free light chain levels. We report here a refinement of this method using latex agglutination techniques. This new method enables quantitative measurement of free light chains in serum at levels as low as 1 mg/l and may allow the clinical application of serum free light chain estimation.

Adult↗

Characterization of cyclic AMP phosphodiesterase isozymes in rat parotid gland.

Cyclic AMP phosphodiesterase (PDE) isozymes were isolated and characterized from the soluble fraction of rat parotid gland. Four main peaks containing PDE activity were obtained by Q-Sepharose Fast Flow column chromatography. The four peaks were identified as PDEs I-IV by kinetic properties, molecular-weight analysis and their responses to effectors and inhibitors.

3',5'-Cyclic-AMP Phosphodiesterases↗

Genital bleeding in premenarcheal children.

OBJECTIVE: The earlier occurrence of secondary sexual development and the advance in diagnostic techniques prompted us to review our recent experience with genital bleeding in childhood. METHOD: We analyzed data for all patients aged less than 10 years who were referred to Gifu University School of Medicine-affiliated hospitals from 1984 through 1993. RESULTS: From a total of 330 girls, 62 (approximately 20%) complained of genital bleeding. The patients were distributed equally between 0 and 10 years of age. In 46 of 62 patients (74%), bleeding resulted from a local lesion of the vagina: 28 due to vulvovaginitis, six to urethral prolapse, six to trauma, three to foreign bodies and three to vaginal tumors. Malignant vaginal tumors were seen in two patients: sarcoma botryoides and endodermal sinus tumor. Both were diagnosed by histopathological examination of an exophytic vaginal tumor, with several weeks' interval from the initial episode of bleeding to diagnosis. The remaining 16 patients (26%), with no demonstrable local lesions, bled as a result of some form of precocious puberty. In six patients, precocious puberty was secondary to a hormonally active ovarian tumor, five of these patients also experiencing advanced breast development. Routine ultrasound and hormonal evaluations promptly detected the presence of tumor. None of three patients with idiopathic precocious puberty presented with secondary sexual development. No specific etiology was established in seven patients. CONCLUSION: Genital bleeding alerts us to the possibility, though rare, of a genital tract tumor. Prompt and precise detection may lead to cure and preservation of future fertility.

Age Distribution↗

A frame-shift mutation of the androgen receptor gene in a patient with receptor-negative complete testicular feminization: comparison with a single base substitution in a receptor-reduced incomplete form.

Mutations of the androgen receptor that impair the action of androgens result in abnormal male sexual development. We studied the structure of the androgen receptor gene in a patient with the receptor-negative form of complete testicular feminization and another patient with a receptor-reduced form of incomplete testicular feminization. In the subject with complete testicular feminization, the deletion of a single nucleotide occurred at nucleotide number 1893 at exon 2. The subsequent frame-shift mutation changes the sense of codon 622 from cysteine to a translational stop signal. Codon 622 is exon 3, so the mutation predicts the synthesis of a truncated receptor that lacks the entire androgen-binding domain. Analysis of a subject with incomplete testicular feminization revealed a single substitution (CGT --> CAT) at nucleotide 2675 of exon 7, resulting in the conversion of an arginine at amino acid 840 to a histidine. This mutation in the androgen-binding domain may impair, but not remove, the androgen binding to its receptor. These results suggest that the phenotypes in our subjects are due to the mutations, and that single amino acid substitution and premature termination codon can cause variably severe functional abnormalities.

Adult↗

[Antineuronal autoantibody to a 40-kDa protein in a patient with cerebellar ataxia and breast cancer].

A 49-year-old woman was admitted to Utsunomiya Saiseikai hospital complaining of right breast swelling. There was half a year history of difficulty in walking. A diagnosis of breast cancer was made by biopsy. Neurological examination revealed scanning speech, nystagmus, intention tremor and ataxic gait, but brain CT scan and MRI showed neither metastatic, invasive lesions nor atrophy in the brain. Lumpectomy for breast cancer was performed. For immunocytochemical studies, the cytoplasm of neurons in sections of normal human cerebral cortex, cerebellum, spinal cord and dorsal root ganglia were stained by the patient's serum, but glial cells were not. Upon Western blot, the patient's serum reacted with a 40-kDa protein in extracts of both cerebrum and cerebellum obtained from normal rats. A diagnosis of paraneoplastic cerebellar degeneration (PCD) was made on the basis of clinical manifestations and detection of the antineuronal antibody. The antibody accompanying the breast cancer which stained neuronal cytoplasm and bound to a 40-kDa protein may be a subtype of antibody causing PCD.

Autoantibodies↗

Possible evidence that the herbal medicine shakuyaku-kanzo-to decreases prostaglandin levels through suppressing arachidonate turnover in endometrium.

The herbal medicine shakuyaku-kanzo-to has been used for the treatment of dysmenorrhea. We attempted to establish the effects of shakuyaku-kanzo-to on prostaglandin (PG) levels and the turnover of arachidonic acid in endometrial cells. Human endometrial cells isolated from proliferative-phase endometria were examined. Arachidonic acid reacylation activity was determined by [3H]arachidonic acid incorporation into endometrial cell phospholipid. Its deacylation rate was determined by both 3H-liberation from [3H]-arachidonic acid-labelled phospholipids and production of lyso-phospholipid. [3H]-PG levels were also analyzed. Shakuyaku-kanzo-to enhanced the rate and maximal level of arachidonic acid incorporation by 1.5-fold into phosphatidyl-ethanolamine and phosphatidylcholine. Degradation of the phospholipids to liberate arachidonic acid and lyso-derivatives was not affected by the shakuyaku-kanzo-to. Shakuyaku-kanzo-to decreased PG levels by approximately 50% of control. Because shakuyaku-kanzo-to stimulates arachidonic acid esterification to phospholipids, it seems likely that shakuyaku-kanzo-to depletes cellular free arachidonic acid with a consequent suppression of prostaglandin synthesis. Shakuyaku-kanzo-to may exert its action against dysmenorrhea through preventing prostaglandin production.

Anti-Inflammatory Agents, Non-Steroidal↗

Fetal blood sampling in the assessment of acute nonimmune hydrops fetalis.

Nonimmune hydrops fetalis can be associated with many fetal conditions. A fetal blood sample obtained from ultrasound-guided cordocentesis can offer vital information about the underlying cause of the nonimmune hydrops fetalis, and perinatal management can be planned accordingly. We attempted to evaluate a case of nonimmune hydrops fetalis conveying poor perinatal outcome through serial fetal blood sampling. Although we could establish no apparent reason for this acute case, fetal blood sampling in addition to ultrasonographic screening can play a key role in the management of the 'perplexing' nonimmune hydrops fetalis.

Adult↗

Primary brain malignant lymphoma newly diagnosed during pregnancy.

Clinical brain tumors become symptomatic or show acceleration of symptoms in pregnant women less often when compared with those in non-pregnant women. We describe the clinical findings and MR imaging of a rare case of malignant lymphoma arising in the brain of a pregnant woman.

Adult↗

Ultrasound-detected polycystic ovarian syndrome associated with depleted basal level but enhanced response of gonadotropin.

A patient with ultrasound-detected polycystic ovaries and anovulatory oligomenorrhea had extremely low luteinizing hormone (LH) levels, but a heightened sensitivity to gonadotropin-releasing hormone (GnRH). Of interest is the finding of undetectable basal LH levels. This rare presentation may suggest that polycystine ovarian syndrome (PCOS) features may be a consequence of the increased response of LH, independently on basal levels of LH.

Adult↗

Regulation of cAMP phosphodiesterases by cyclic nucleotides in rat parotid gland.

Approximately 88% of the total cAMP phosphodiesterase (PDE) activity was detected in the supernatant fraction of the rat parotid homogenate. Mono Q ion-exchange chromatography revealed five main peaks (PDE I, PDE II, PDE III, PDE IV and unknown). A high concentration of cGMP (> 1 microM) was necessary to activate PDE II, whereas PDE III was inhibited by cGMP at a concentration that was 1,000 times lower (100 pM). PDEs III and IV were activated by treatment with a catalytic subunit of cAMP-dependent protein kinase (A kinase), and H-8, a A kinase inhibitor, inhibited the activation. Treatment of parotid slices with 1 microM isoproterenol stimulated PDE activity by approximately 120%, and 10 microM propranolol inhibited the activation.

3',5'-Cyclic-AMP Phosphodiesterases↗

Ultrasonographic images of tongue movement during mastication.

We observed vertical motion of the tongue during mastication in ultrasonographic images of 6 males with an average age of 28.7 years. All subjects had complete dentition and no evidence of neurological disorders. We used a 7 MHz mechanical convex scanning transducer to obtain a continuous, real-time ultrasonic image of the tongue, and carried out real-time B-mode ultrasonic observation at the median sagittal plane of the mandible. We recorded vertical motion of the tongue in the M-mode on a line connecting the mandibular first molars. The transducer produced good quality images of the dorsal surface during mastication of peanuts, rice, crackers, boiled fish paste, pickled radishes, pudding and bananas. The transducer, which was small and light, permitted capture of the images on videotape without manual placement of the scanner. Continuous images showed that the tongue turned the food, mixed it with saliva, sorted out unsuitable particles and aided in bolus formation. Vertical motion of the tongue had two phases, sorting and bolus formation.

Adult↗

Effect of thyrotropin-releasing hormone (TRH) on cerebral blood flow in spinocerebellar degeneration and cerebrovascular disease.

The effect of TRH on cerebral blood flow in patients with spinocerebellar degeneration and cerebrovascular disease was investigated. Cerebral blood flow was measured by the 133Xenon arterial injection method before, and 30 min after, the intravenous administration of 1000 micrograms of TRH. TRH had no effect on mean arterial blood pressure in either group. In the spinocerebellar degeneration group, cerebral blood flow increased slightly after the injection of TRH, from 52.7 +/- 10.5 to 56.7 +/- 16.0 ml/100 g brain/min. In two patients with spinocerebellar degeneration, whose autonomic function was normal and whose brainstem structure appeared normal in the CT scan, cerebral blood flow increased from 54.8 to 66.4 ml (21.2%), and from 68.6 to 79.9 ml (16.5%), respectively. In the patients with cerebrovascular disease, cerebral blood flow did not change (49.7 +/- 10.8 ml before and 49.4 +/- 12.6 ml after TRH). Cerebral blood flow reportedly increases following an intravenous injection of TRH in animals, supposedly due to the activation of intrinsic cerebral vasodilative fibers situated in the submesencephalic brainstem region. Our results are consistent with this hypothesis and with the clinical finding that TRH especially improves ataxia in spinocerebellar degeneration where there is no pyramidal involvement or disorder of deep sensation.

Autonomic Nervous System↗

Gonadotropin-releasing hormone receptor in gynecologic tumors. Frequent expression in adenocarcinoma histologic types.

BACKGROUND: Gonadotropin-releasing hormone (Gn-RH) analogs have been used in the therapy of the endocrine-dependent cancers. The authors attempted to determine the frequency with which Gn-RH receptor (Gn-RHR) is present in gynecological cancers. METHODS: Experiments were performed on gynecologic tumors that had been surgically removed and their cloned cell lines. Gn-RHR was characterized by [3H]Gn-RH binding to plasma membrane preparations. Gn-RHR messenger ribonucleic acid was determined by reverse transcription-polymerase chain reaction using oligonucleotide primers synthesized according to the published human Gn-RHR sequence. RESULTS: High affinity binding sites with nanomolar range of Kd and Gn-RHR mRNA were detected in a high proportion (over 90%) of the specimens from endometrium (6 of 6) and endometrial carcinomas (16 of 17), myometrium (6 of 6) and myomas (4 of 5), epithelial carcinoma (21 of 23), and stromal tumors (3 of 3) of the ovary. There was no substantial Gn-RHR in cervical carcinomas or germ cell-derived tumors of the ovary. Cloned cell lines gave identical results to those obtained in their respective mother tumors. CONCLUSIONS: We detected Gn-RHR in a wide range of the carcinomas and tissues originating from the endometrium and ovary, but not in the uterine cervix or germ cell-derived tumors. The expression of Gn-RH receptor raises the possibility that Gn-RH may play a direct regulatory role in the growth of these carcinomas, and provides a possible point of attack for therapeutic approaches using Gn-RH analogs in these malignancies.

Adenocarcinoma↗